Effect of lipopolysaccharide on the permeability and reactivity of the cerebral microcirculation: role of inducible nitric oxide synthase

Brain Res. 1998 May 11;792(2):353-7. doi: 10.1016/s0006-8993(98)00259-5.

Abstract

The goal of this study was to examine the effect of lipopoly saccharide on the permeability of the blood-brain barrier and reactivity of cerebral arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier (clearance of fluorescent-labeled dextran; molecular weight 10,000 Da; FITC-dextran-10K) and diameter of pial arterioles were measured in the absence and presence of topical application of vehicle (saline) or lipopolysaccharide (200 ng/ml). During superfusion with vehicle, clearance of FITC-dextran-10K from pial vessels was minimal, and diameter of pial arterioles remained constant. Topical application of lipopolysaccharide (200 ng/ml) produced an increase in clearance of FITC-dextran-10K and dilated pial arterioles. To determine whether lipopolysaccharide-induced changes in permeability of the blood-brain barrier and dilatation of cerebral arterioles was related to the synthesis/release of inducible nitric oxide, we examined the effects of aminoguanidine (0.5 mM). Aminoguanidine inhibited lipopolysaccharide-induced increases in permeability of the blood-brain barrier and dilatation of cerebral arterioles. The findings of the present study suggest that lipopolysaccharide increases permeability of the blood-brain barrier and diameter of pial arterioles via the activation of inducible nitric oxide synthase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arterioles / drug effects
  • Arterioles / enzymology
  • Bacterial Infections / metabolism
  • Blood-Brain Barrier / drug effects*
  • Brain / blood supply
  • Brain / enzymology
  • Cerebrovascular Circulation / drug effects*
  • Dextrans / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Fluorescein-5-isothiocyanate / analogs & derivatives*
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Guanidines / pharmacology
  • Lipopolysaccharides / pharmacology*
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / physiology*
  • Nitric Oxide Synthase Type II
  • Pia Mater / blood supply
  • Pia Mater / enzymology
  • Rats
  • Rats, Inbred WF
  • Venules / drug effects
  • Venules / enzymology

Substances

  • Dextrans
  • Enzyme Inhibitors
  • Guanidines
  • Lipopolysaccharides
  • fluorescein isothiocyanate dextran
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Fluorescein-5-isothiocyanate
  • pimagedine